FIG. 1.

The effect of high-fat (HF) feeding on liver NO, hepatic inflammation, and Kupffer cell activation. Wild-type (WT) mice were fed either a low-fat (LF) or HF diet for 2, 4, or 8 weeks. A: Hepatic NO content during HF and LF feeding as measured by electron spin resonance spectroscopy (n = 9). B: Liver eNOS phosphorylation of Ser 1177 as measured by Western blot (n = 9). C: Liver phospho–IκB-α as measured by Western blot, normalized to total GAPDH levels (n = 9). D: Liver IL-6. E: TNF-α mRNA (n = 9). F: ICAM mRNA levels (n = 9). G: Relative mRNA levels from isolated Kupffer cells as measured by RT-PCR after 2, 4, and 8 weeks of LF or HF diet (n = 5 mice). H: In parallel experiments in WT mice, hepatic insulin signaling was assessed following intraperitoneal injection of insulin or saline vehicle (n = 5 per group). Liver protein lysates were analyzed for IRS-1 tyrosine phosphorylation (p–IRS-1), IRS-1, pAkt, and Akt levels by enzyme-linked immunosorbent assay. *P < 0.05.